Download Full Text PDF

1
1
Development and Spontaneous Resolution of Suppurative
Granulomatous Inflammation of Glans Penis Following
Intravesical Administration of Bacillus Calmette-Guerin
Yu-Hao Chang
Chi-Jung Chung
Tseng-tong Kuo1
Hong-Shang Hong
A 57-year-old male was found to have papillary transitional cell carcinoma of the urinary bladder
and underwent a tranurethral resection of the tumor. He suffered from multiple asymptomatic red
papules on glans penis after 9 th intravesical therapy with Bacillus Calmette - Guerin ( BCG ). His left
inguinal lymph node was enlarged and tender. The skin lesions were found to be due to suppurative
granulomatous inflammation. Periodic acid-Schiff stain (PAS) and acid-fast stain (AFS) were negative. The lesions on glans penis and the enlarged inguinal lymph node resolved spontaneously few
weeks later. The occurrence of granulomatous cutaneous lesions following BCG therapy is reported.
(Dermatol Sinica 22 : 231-234, 2004)
Key words: Bacillus Calmette-Guerin (BCG), Glans penis
57
PAS
(
AFS
22 : 231 - 234, 2004 )
From the Departments of Dermatology and Pathology,1 Chang Gung Memorial Hospital-Taipei
Accepted for publication : February 12, 2004
Reprint requests: Chi-Jung Chung M.D., Department of Dermatology, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road,
Taipei, Taiwan
TEL: 886-2-27135211 ext. 3397 FAX: 886-2-27191623
231
INTRODUCTION
Intravesical therapy with Bacillus Calmette
-Guerin (BCG) has proved to be effective in the
prophylaxis and treatment of superficial urinary
bladder tumors and carcinoma in situ. 1 The
increasing use of this treatment has been accompanied by reports of local and systemic complications.2 To our knowledge, only 6 reports of
BCG related penile or urethral infection have
been published before.3 - 7 We describe a patient
with BCG related glans penis granulomatous
inflammation following intravesical therapy for
a superficial transitional cell carcinoma and
review the related literature.
CASE REPORT
A 57-year-old man with a history of cigarette smoking presented at our outpatient clinic
in May 2001 with painless hematuria. Cystoscopy revealed a 0.5 cm papillary tumor at left
ureteral orifice. Tranurethral resection of the
tumor was performed and the tumor was a grade
I transitional cell carcinoma. Intravesical BCG
immunotherapy started in June 2001. He
received a total of 8 instillations at weekly intervals from June 2001 to September 2001. The
course was quite smooth except an episode of
cystitis after 7 th instillation. However, several
asymptomatic red papules developed on the
glans penis 3 days later after the 9 th instillation.
The papules were erythematous with 2~3 mm
deep - seated white pustules ( Fig. 1 ). Besides, a
2 x 2 cm tender lymph node was noted on the
left inguinal area. There were no other abnormalities in physical examinations. A biopsy
specimen of the skin lesions showed granuloma
with central microabscess in the dermis (Fig. 2a,
2b ). Special stains with Periodic acid - Schiff
stain ( PAS ) and acid - fast stain ( AFS ) were
negative. His chest X-ray was normal and laboratory tests including a complete blood cell
count and blood chemistry were all within normal limits. The test for mycobacterial DNA by
polymerase chain reaction was negative.
Although only topical antibiotics was prescribed, the lesions spontaneously healed with-
Fig. 2a
Photomicrography showed a dermal granuloma with central
microabscess formation. (H & E, x40)
Fig. 1
Fig. 2b
The clinical appearance of multiple discrete erythematous
papules on the glans penis induced by intravesical
immunotherapy with BCG
A multinucleated giant cell (arrow) (H & E x400)
Dermatol Sinica, September 2004
232
out scarring in two weeks. The left inguinal
lymphoadenopathy also resolved later.
DISCUSSION
BCG is the attenuated strain of bovine bacterium tuberculosis and consists of living bacilli,
dead microorganisms and subcellular debris. It
is thought to act as a potent stimulator of local
cellular immunity.1 Intravesical instillation of
BCG has been shown to serve as an effective
treatment of and prophylaxis for recurrent stage
Ta and T1 tumors and carcinoma in situ. The
increased use of this treatment has been accompanied by reports of local and systemic complications. In the study of 2,602 patients by Lamm
et al,2 high fever (greater than 39˚C) occurred in
2.9 % of the patients, granulomatous prostatitis
in 0.9 %, granulomatous pneumonitis and / or
hepatitis in 0.7%, arthralgia in 0.5%, hematuria
in 1%, skin rash in 0.3%, ureteral obstruction in
0.3%, epididymitis in 0.4%, contracted bladder
in 0.2%, renal abscess in 0.1%, sepsis in 0.4%
and cytopenia in 0.1%. In general, 95% of the
patients have no serious side effects. Traumatic
catheterization or concurrent cystitis is the
major risk factor for systemic BCG absorption.
BCG related penile or urethral infection
was quite rare. To our knowledge only 6 cases
have been previously published in the literature.
3-7
The clinical presentations include painful erythematous papules, crusty ulcers, palpable dorsal penile nodules combine with coronal abscess
and penile edema associate with meatal ulceration. These cutaneous lesions were noted
between 7~15 days following intravesical BCG
instillation. Enlarged inguinal lymph nodes were
most often noted. Only three cases underwent
skin biopsy. Tuberculoid granuloma was the
common histopathologic finding. But none of
them demonstrated acid - fast bacilli. M. bovisBCG was identified by tissue culture only in
two cases and M. tuberculosis was found in the
case reported by Konohana et al.3, 5, 7 Under the
treatment of combinative antituberculous
chemotherapy, the lesions of these 6 cases
resolved gradually in few months later.
The clinical picture and histopathologic
233
finding in our patient was similar to the case
reported by Ribera et al.5 Asymptomatic erythematous papules with central whitish pustules on
the glans penis combined with inguinal lymphadenopathy following intravesical immunotherapy were characteristic clinically sufficient to suggest the diagnosis. Because the
patient refused another skin biopsy for tissue
culture, we tried to examine mycobacterial
DNA by polymerase chain reaction. However,
the result was negative. According to the study
concerning the fate of bacillus Calmette-Guerin
after intravesical instillation by Durek et al,8
mycobacterial DNA was found only in 31.8 %
bladder biopsies obtained within one week after
the last installation. Purified protein derivative
(PPD) skin test was not performed in this case
unfortunately. The conversion from a negative
to positive tuberculin skin test can help to confirm a recent mycobacteria infection. With the
clinical charateristics and pathological findings,
we favor this is a case of BCG related balanitis
after intravesical immunotherapy.
The differential diagnosis of similar penis
lesions must include lichen nitidus, ectopic
sebaceous gland and papulonecrotic tuberculid.
Lichen nitidus is composed of discrete smooth,
flat, round papules with flesh-colored and glistening appearance. Each papule consists of a
well - circumscribed mixed - cell granulomatous
infiltrate in an expaned dermal papilla. Ectopic
sebaceous glands are asymptomatic yellowish
papules on the inner aspect of the prepuce and
rarely on the glans penis. Each globoid lesion
consists of a group of small but mature sebaceous lobules situated around a small sebaceous
duct leading to the surface epithelium.
Isrealewicz et al. reported a case of papulonecrotic tuberculid with penis involvement.
Penile lesions combined with multiple punchedout scars on the leg was the clinical finding.9
Classically, the infectious complications of
BCG therapy were treated with isoniazid 300mg
daily. If there was no response, rifampicin
600mg daily was added. The previous 6 reports
of BCG related penile or urethral infection were
all treated with combination antituberculous
Dermatol Sinica, September 2004
chemotherapy. The skin lesions and inguinal
lymphadenopathy all resolved gradually. In our
case, the lesions healed spontaneously in two
weeks although only topical antibiotic was prescribed. Following the management of adverse
reactions to BCG vaccination in literature
reviews, conservative therapeutic approach is
usually adequate. Prescription of isoniazid for
the benefit in local abscess resolution is still
controversial. Such therapy is only considerated
unless there is clear evidence of suppurative
reaction associated lymphadenopathy. 10 In a
review of incidence and treatment of complications of BCG intravesical therapy of 2602
patients, 300mg isoniazid orally was recommened for 3 months in patients with persistent
fever for 12 ~ 24 hours. The combination of
300mg isoniazid , 600mg rifampin and 1200mg
ethembutol for 6 months is indicated in patients
with systemic side effects or sepsis.2 We report a
case of BCG - related balanitis resolved spontaneously without using antituberculous chemotherapy.
According to the definition in textbooks,
tuberculosis of the skin is caused by M. tuberculosis and M. bovis, including bacillus CalmetteGuerin ( BCG ).11 Although different titles were
used in the previous 6 reports of BCG related
penile infection, 3 - 7 penile tuberculosis after
intravesical bacillus Calmette-Guerin treatment
may be a more accurate description. For lacking
direct evidence to prove the presence of
mycobacteria bovis in skin rash of this case, our
title was mainly according to the histopathologic finding.
REFERENCE
Mechanisms of action of intravesical bacille
Calmette-Guerin: Local immune mechanisms.
Clin Infect Dis 31: 91-93, 2000.
2. Lamm DL, Morales A, Brosman SA, et al.:
Incidence and treatment of complications of bacillus Calmette-Guerin intravesical therapy in superficial bladder cancer. J Urol 147: 596-600, 1992.
3. Konohana A, Noda J, Shoji K, et al.: Primary
tuberculosis of the glans penis. J Am Acad
Dermatol 26: 1002-1003, 1992.
4. Erol A, Ozgur S, Tahtall N, et al.: Bacillus
Calmette-Guerin(BCG) balanitis as a complication
of intravesical BCG immunotherapy. Int Urol
Nephrol 27: 307-310, 1995.
5. Ribera M, Bielsa J, Manterola JM, et al.:
Mycobacterium bovis-BCG infection of the glans
penis: a complication of intravesical administration of bacillus Calmette-Guerin. Br J Dermatol
132: 309-310, 1995.
6. Baniel J, Lev Z, Engelstein D, et al.: Penile edema
and meatal ulceration after intravesical instillation
with bacillus Calmette-Guerin. Urology 47: 932934, 1996.
7. Latini JM, Wang DS, Forgacs P, et al.: Tuberculosis of the penis after intravesical bacillus Calmette
-Guerin treatment. J Urol 163: 1870, 2000.
8. Durek C, Richter E, Basteck A, et al.: The fate of
bacillus Calmette-Guerin intravesical Installation.
J Urol 165: 1765-1768, 2001.
9. Isrealewicz S, Dharan M, Rosenman D, et al.:
Papulonecreotic tuberculid of the glans penis. J
Am Acad Dermatol 12: 1104-1106, 1985.
10. FitzGerald JM: Management of adverse reaction
to bacille Calmette-Guerin vaccine. Clin Infect
Dis 31: 75-76, 2000.
11. Tappeiner G, Wolff K: Tuberculosis and other
mycobacterial infections. In: Freedberg IM, Eisen
AZ, Wolff K et al., eds. Dermatology in General
Medicine. 5th ed. New York: McGraw-Hill, 22742292, 1999.
1. Prescott S, Jackson AM, Hawkyard SJ, et al.:
Dermatol Sinica, September 2004
234